The identification of new pharmacophores is of paramount biomedical importance and natural products have recently been regaining attention for this endeavor.1 This renaissance is closely tied to the successful exploitation of the marine environment which harbors unmatched biodiversity that is presumably concomitant with chemical diversity.2 In particular, marine cyanobacteria are prolific producers of bioactive secondary metabolites,3 many of which are modified peptides or peptide—polyketide hybrids with promising antitumor activities, such as dolastatin 10,4 curacin A,5 and apratoxin A.6 As a result of ongoing investigations to identify new drug leads from cyanobacteria in Florida, we report here the structure determination and preliminary biological characterization of a marine cyanobacterial metabolite with novel chemical scaffold and nanomolar antiproliferative activity. These findings provide new alternatives to address unmet needs in the treatment of proliferation diseases and disorders. The compounds herein are also now found to mediate histone deacetylase (HDAC) processes (e.g., inhibition) and as such are useful for treating diseases, disorders, or symptoms thereof mediated by inhibition of histone deacetylase (HDAC). These findings provide new alternatives to address unmet needs in the treatment of HDAC mediated diseases and disorders.